In order to explore the modulating role of the IL-6 axis on CD4+ T cell subsets we will investigate total CD4 and CD4 subsets, examine expression of IL-6R and gp130 on CD4+ T cells and subsets and assess IL-6, soluble IL-6R and soluble gp130 (inhibitor of IL-6 signaling) in sera of the participating cohorts. We will assess the effect of both the classical IL-6R signaling and IL-6 trans signaling pathways (IL-6+sIL-6R) on naïve T cell activation, proliferation and Th1/Th17 skewing potential and on Treg dysregulation. Bio repositories and patient cohorts
GCA, healthy control and RA cohort
Unique cohorts of newly-diagnosed, untreated GCA patients have been built at the UMCG Vasculitis Expertise Centre. From these patients serial blood samples/ peripheral blood mononuclear cells PBMCs at the time of diagnosis and at regular intervals at follow up have been prospectively collected and bio-banked (total cohort contains more than 100 patients and inclusion and follow up is ongoing) . Treatment is done according to a fixed protocol including tocilizumab which has recently been registered for GCA. Our SENEX cohort including around 100 aged individuals serves as a healthy, age-matched control group. For RA we have a unique follow up cohort of patients at risk for RA defined as autoantibody ( ACPA+ and/or RF+) positive patients without arthritis. During follow up 40% of RA risk patients developed RA. We also have stored PBMC samples from seropositive RA (ACPA+ and/or RF+) patients and recently diagnosed seronegative ( ACPA- and RF-) RA patients (more than 150 patients in total).
In the second part of this project the discovered inflammatory signatures will be measured in patients with type 2 diabetes. We manage a large observational study of patients with type 2 diabetes in primary care in Groningen. A total of 903 patients are participating in this study. Blood and urine samples are collected at baseline and at annual visits. In a sub group of patients also PBMCs will be collected. The follow-up duration ranges from 3 to 6 years. This cohort provides a unique opportunity to translate the inflammation signatures from GCA and RA cohorts to diabetes and to test to what extend they are common in both chronic conditions.